CN110402245A - 外消旋3-烷基哌啶-羧酸乙酯的旋光异构体的分离方法 - Google Patents
外消旋3-烷基哌啶-羧酸乙酯的旋光异构体的分离方法 Download PDFInfo
- Publication number
- CN110402245A CN110402245A CN201880017860.2A CN201880017860A CN110402245A CN 110402245 A CN110402245 A CN 110402245A CN 201880017860 A CN201880017860 A CN 201880017860A CN 110402245 A CN110402245 A CN 110402245A
- Authority
- CN
- China
- Prior art keywords
- salt
- hcl
- crystallization
- racemic
- diastereoisomeric
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000003287 optical effect Effects 0.000 title claims abstract description 12
- 125000004494 ethyl ester group Chemical group 0.000 title claims abstract description 10
- 238000000926 separation method Methods 0.000 title claims description 7
- 238000000034 method Methods 0.000 claims abstract description 48
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 14
- RGHNJXZEOKUKBD-QTBDOELSSA-N L-gulonic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O RGHNJXZEOKUKBD-QTBDOELSSA-N 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims description 88
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 42
- 239000003513 alkali Substances 0.000 claims description 35
- 239000000706 filtrate Substances 0.000 claims description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 26
- 238000002425 crystallisation Methods 0.000 claims description 22
- 230000008025 crystallization Effects 0.000 claims description 22
- 230000008569 process Effects 0.000 claims description 20
- 150000003840 hydrochlorides Chemical class 0.000 claims description 14
- 238000001953 recrystallisation Methods 0.000 claims description 14
- 238000001704 evaporation Methods 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 12
- 230000008020 evaporation Effects 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- 238000001914 filtration Methods 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 238000012545 processing Methods 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 238000009835 boiling Methods 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims 4
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims 2
- 230000003044 adaptive effect Effects 0.000 claims 1
- 239000000010 aprotic solvent Substances 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 claims 1
- 238000006731 degradation reaction Methods 0.000 claims 1
- 239000002054 inoculum Substances 0.000 claims 1
- 229940011051 isopropyl acetate Drugs 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000012071 phase Substances 0.000 description 7
- 238000005194 fractionation Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000004519 grease Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- -1 compound nipecotic acid ethyl esters Chemical class 0.000 description 4
- 230000001376 precipitating effect Effects 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 241000208340 Araliaceae Species 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 3
- 235000003140 Panax quinquefolius Nutrition 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 235000008434 ginseng Nutrition 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- 230000001172 regenerating effect Effects 0.000 description 3
- 238000010583 slow cooling Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- KGPORUPPPXXHGA-UHFFFAOYSA-N 1-(3-propan-2-ylphenyl)piperidine Chemical class CC(C)C1=CC=CC(N2CCCCC2)=C1 KGPORUPPPXXHGA-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229960001367 tartaric acid Drugs 0.000 description 2
- WASODVRPQOPBAI-UHFFFAOYSA-N 1-tert-butyl-3-ethylpiperidine Chemical compound CCC1CCCN(C(C)(C)C)C1 WASODVRPQOPBAI-UHFFFAOYSA-N 0.000 description 1
- KLJFVHYXYOEZCA-UHFFFAOYSA-N 3-ethylpiperidine-3-carboxylic acid Chemical compound CCC1(C(O)=O)CCCNC1 KLJFVHYXYOEZCA-UHFFFAOYSA-N 0.000 description 1
- DEMOKNSWMVAJPZ-UHFFFAOYSA-N 3-methylpiperidin-1-ium-3-carboxylate Chemical compound OC(=O)C1(C)CCCNC1 DEMOKNSWMVAJPZ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-CBPJZXOFSA-N D-Gulose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-CBPJZXOFSA-N 0.000 description 1
- 229940091860 GABA uptake inhibitor Drugs 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 239000000064 cholinergic agonist Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000002843 gaba uptake inhibitor Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D9/005—Selection of auxiliary, e.g. for control of crystallisation nuclei, of crystal growth, of adherence to walls; Arrangements for introduction thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B63/00—Purification; Separation; Stabilisation; Use of additives
- C07B63/04—Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU1700109A HU231150B1 (hu) | 2017-03-13 | 2017-03-13 | Eljárás racém 3-alkilpiperidin-3-karbonsav-etil-észterek optikai izomerjeinek elválasztására |
| HUP1700109 | 2017-03-13 | ||
| PCT/IB2018/051600 WO2018167631A1 (en) | 2017-03-13 | 2018-03-12 | Process for the separation of optical isomers of racemic 3-alkylpiperidine-carboxylic acid ethyl esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110402245A true CN110402245A (zh) | 2019-11-01 |
Family
ID=89992390
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201880017860.2A Pending CN110402245A (zh) | 2017-03-13 | 2018-03-12 | 外消旋3-烷基哌啶-羧酸乙酯的旋光异构体的分离方法 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US11091436B2 (hu) |
| EP (1) | EP3596048A1 (hu) |
| JP (1) | JP2020511453A (hu) |
| KR (1) | KR20190128663A (hu) |
| CN (1) | CN110402245A (hu) |
| AR (1) | AR111273A1 (hu) |
| AU (1) | AU2018235267A1 (hu) |
| BR (1) | BR112019018847A2 (hu) |
| CA (1) | CA3056189A1 (hu) |
| CO (1) | CO2019010117A2 (hu) |
| EA (1) | EA201992050A1 (hu) |
| HU (1) | HU231150B1 (hu) |
| MX (1) | MX2019011001A (hu) |
| WO (1) | WO2018167631A1 (hu) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW202220992A (zh) | 2020-08-05 | 2022-06-01 | 匈牙利商羅特格登公司 | 具藥理活性之經雜環取代的吡唑并〔１，５－ａ〕嘧啶衍生物 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3904632A (en) * | 1972-05-08 | 1975-09-09 | Hoffmann La Roche | (')-di-o-isopropylidene-2-keto-l-gulonates |
| US5721250A (en) * | 1993-12-23 | 1998-02-24 | Merck & Co. Inc. | Di-and tri-substituted piperidines, pyrrolidines and hexahydro-1H-azepines promote release of growth hormone |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL322706A1 (en) | 1993-11-09 | 1998-02-16 | Merck & Co Inc | Piperidines, pyrolidines and hexahydro-1h-azepins enhancing growth hormone liberation |
| US5492916A (en) | 1993-12-23 | 1996-02-20 | Merck & Co., Inc. | Di- and tri-substituted piperidines, pyrrolidines and hexahydro-1H-azepines promote release of growth hormone |
| US6362188B1 (en) | 1998-12-18 | 2002-03-26 | Schering Corporation | Farnesyl protein transferase inhibitors |
| BR9916328A (pt) | 1998-12-18 | 2001-10-02 | Schering Corp | Inibidores de transferase de farnesila |
| CO5150225A1 (es) | 1999-03-19 | 2002-04-29 | Merck Sharp & Dohme | Derivados del tetrahidropirano y su uso como agentes terapeuticos |
| WO2008117982A1 (en) | 2007-03-28 | 2008-10-02 | Crystal Genomics, Inc. | Heterocyclic carboxylic acid derivatives and pharmaceutical composition for inhibiting lipid accumulation containing same |
| TW200938200A (en) * | 2007-12-28 | 2009-09-16 | Dainippon Sumitomo Pharma Co | Methyl-substituted piperidine derivative |
| EP2261210B1 (en) | 2008-02-06 | 2014-10-22 | Msd K.K. | 3-substituted sulfonyl piperazine derivative |
-
2017
- 2017-03-13 HU HU1700109A patent/HU231150B1/hu not_active IP Right Cessation
-
2018
- 2018-03-12 JP JP2019549364A patent/JP2020511453A/ja active Pending
- 2018-03-12 AU AU2018235267A patent/AU2018235267A1/en not_active Abandoned
- 2018-03-12 WO PCT/IB2018/051600 patent/WO2018167631A1/en unknown
- 2018-03-12 CN CN201880017860.2A patent/CN110402245A/zh active Pending
- 2018-03-12 EP EP18713017.4A patent/EP3596048A1/en not_active Withdrawn
- 2018-03-12 KR KR1020197028840A patent/KR20190128663A/ko not_active Application Discontinuation
- 2018-03-12 CA CA3056189A patent/CA3056189A1/en active Pending
- 2018-03-12 MX MX2019011001A patent/MX2019011001A/es unknown
- 2018-03-12 EA EA201992050A patent/EA201992050A1/ru unknown
- 2018-03-12 BR BR112019018847A patent/BR112019018847A2/pt not_active Application Discontinuation
- 2018-03-12 US US16/493,449 patent/US11091436B2/en active Active
- 2018-03-13 AR ARP180100582A patent/AR111273A1/es unknown
-
2019
- 2019-09-18 CO CONC2019/0010117A patent/CO2019010117A2/es unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3904632A (en) * | 1972-05-08 | 1975-09-09 | Hoffmann La Roche | (')-di-o-isopropylidene-2-keto-l-gulonates |
| US5721250A (en) * | 1993-12-23 | 1998-02-24 | Merck & Co. Inc. | Di-and tri-substituted piperidines, pyrrolidines and hexahydro-1H-azepines promote release of growth hormone |
Non-Patent Citations (3)
| Title |
|---|
| CURT PETTERSSON，等: "Chiral Separation of Amines Using Reversed-Phased Ion-Pair Chromatography", 《CHIRALITY》 * |
| NIKOLETTA B. BA´THORI，等: "One hydrogen bond does not a separation make,or does it? Resolution of amines by diacetoneketogulonic acid", 《CHEM. COMMUN.》 * |
| ROBERT FITZI，等: "Resolution and use in α-amino acid synthesis of imidazolidinone glycine derivatives", 《TETRAHEDRON》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| HU231150B1 (hu) | 2021-03-29 |
| AR111273A1 (es) | 2019-06-26 |
| US11091436B2 (en) | 2021-08-17 |
| CO2019010117A2 (es) | 2019-10-09 |
| BR112019018847A2 (pt) | 2020-04-14 |
| HUP1700109A1 (en) | 2018-09-28 |
| JP2020511453A (ja) | 2020-04-16 |
| EA201992050A1 (ru) | 2020-02-06 |
| CA3056189A1 (en) | 2018-09-20 |
| EP3596048A1 (en) | 2020-01-22 |
| AU2018235267A1 (en) | 2019-10-17 |
| MX2019011001A (es) | 2019-10-17 |
| KR20190128663A (ko) | 2019-11-18 |
| US20200131126A1 (en) | 2020-04-30 |
| WO2018167631A1 (en) | 2018-09-20 |
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